Role of medullary TRH in brain-gut interaction-mediated gastric integrity

摘要

Kainic acid delivered into the raphe pallidus (Rpa) in the medulla increased gastric acid secretion and produced gastric mucosal lesions, which were completely prevented by bilateral microinjection of TRH antibody into the dorsal motor nucleus of the vagus (DMN) in rats. These findings indicated that endogenous TRH action on the DMN may contribute to gastric mucosal lesions. On the contrary, endogenous TRH at a subthreshold dose increasing gastric acid secretion alleviates gastric injury induced by intragastric administration of a strong irritant. The dual action of the medullary TRH on gastric integrity is mediated through activation of peripheral vagal-enteric nervous systems and cholinergic pathways. The outcome reflects the balance between peripheral aggressive and protective factors recruited by the level of vagal cholinergic activation. Subdiaphragmatic vagotomy or intracisternal injection of TRH antibody by itself increased gastric injury induced by a strong irritant and completely abolished theprotective effect of a mild irritant pretreatment in rats. The number of c-fos protein-positive cells in the DMN increased in the process of the adaptive cytoprotection,. These results suggest that vagal afferent nerves activated by gastric topical irritant act on DMN by releasing endogenous TRH to induce gastric protection against the subsequent strong irritant. Medullary TRH and gastric vagal efferent and afferent circuits may play a crucial role in the modulation of gastric integrity.